The streptozotocin-induced rat model of Alzheimer's disease exhibited a blunted heart rate response to low blood pressure and reduced maximal sympathetic nerve activity compared to controls.
Does the STZ-AD rat model exhibit autonomic changes that explain orthostatic hypotension in Alzheimer's disease?
In an Alzheimer's disease rat model, baroreflex function is impaired primarily due to sympathetic nervous system dysfunction, providing a potential mechanism for orthostatic hypotension in human AD.
BACKGROUND: Alzheimer's disease (AD) patients frequently present with orthostatic hypotension. This inability to reflexively increase blood pressure on standing is a serious health concern and increases the risk of stroke and cardiovascular diseases. OBJECTIVE: Since there are no clear mechanisms for orthostatic hypotension in human AD, the present study assessed the autonomic changes that could explain this comorbidity in an AD animal model. METHODS: We used the established streptozotocin-induced rat model of AD (STZ-AD), which mimics many hallmark symptoms of sporadic AD in humans. Baroreflex responses were analyzed in anesthetized STZ-AD rats using femoral catheterization for blood pressure and heart rate, and autonomic activity was assessed using specific blockers and splanchnic sympathetic nerve recordings. Expression levels of autonomic receptors at the heart were examined using the western blot technique. RESULTS: Baroreflex function in STZ-AD showed a blunted heart rate (HR) response to low blood pressure challenges, and the maximal sympathetic nerve activity was reduced. Conversely, HR responses to high blood pressure were similar to control, indicating no change in parasympathetic nerve activity. Under resting conditions, autonomic blockade demonstrated a baseline shift to increased sympathetic tone in STZ-AD. Protein expression levels of beta-1 adrenergic receptor and muscarinic acetylcholine receptor M2 in the heart were unchanged. CONCLUSION: Our study provides the first data on the pathological influence of AD on baroreflex function, which primarily affected the sympathetic nervous system in STZ-AD. These results represent the first mechanisms that may correlate with the orthostatic hypotension in human AD.
Ehlen et al. (Fri,) conducted a other in Alzheimer's disease with orthostatic hypotension. Streptozotocin-induced AD model (STZ-AD) vs. Control was evaluated on Baroreflex responses (heart rate and sympathetic nerve activity). The streptozotocin-induced rat model of Alzheimer's disease exhibited a blunted heart rate response to low blood pressure and reduced maximal sympathetic nerve activity compared to controls.